[In vitro killing effects of STI571 on esophageal carcinoma cell lines CE-48T and CE-81T]

Ai Zheng. 2006 Apr;25(4):456-60.
[Article in Chinese]

Abstract

Background & objective: Tyrosine kinase mediates cell proliferation and differentiation, and plays important roles in tumorigenesis and development of esophageal carcinoma. STI571 is a tyrosine kinase inhibitor of platelet-derived growth factor receptor beta (PDGFR-beta) which is overexpressed in esophageal carcinoma. This study was to explore the in vitro killing effects of STI571 on esophageal carcinoma cell lines CE-48T and CE-81T.

Methods: The expression of PDGFR-alpha and PDGFR-beta in CE-48T and CE-81T cells was detected by Western blot. The killing effects of STI571 on CE-48T and CE-81T cells were evaluated by MTT assay. Cell apoptosis was analyzed by flow cytometry with Annexin V/PI labeling. The expression of p-PDGFR-beta was detected by Western blot before and after treatment of STI571.

Results: CE-48T cells expressed PDGFR-beta, but did not express PDGFR-alpha; CE-81T cells did not express both PDGFR-alpha and PDGFR-beta. The 50% inhibitory concentration (IC50) of STI571 was significantly lower for CE-48T cells than for CE-81T cells [(8.32+/-1.50) micromol/L vs. (41.02+/-7.64) micromol/L, P=0.002]. When treated with 10 micromol/L STI571 for 12 h, the apoptosis rate of CE-48T cells was (52.43+/-5.30)%, but the apoptosis rate did not increase as the treatment time and concentration increased. After treatment of STI571, the expression of p-PDGFR-beta was inhibited in CE-48T cells, but didn't change in CE-81T cells.

Conclusions: STI-571 could induce the apoptosis of PDGFR-beta-positive esophageal carcinoma CE-48T cells. p-PDGFR-beta might be the target of STI571.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Benzamides
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Delivery Systems
  • Esophageal Neoplasms / pathology*
  • Humans
  • Imatinib Mesylate
  • Piperazines / administration & dosage
  • Piperazines / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacology*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta